Human Papillomavirus (HPV) infects the genital tract and has been associated with various dysplasias, cancers, and other diseases. These diseases are currently targets for vaccine development and vaccines containing virus-like particles (VLPs) which contain L1 or the combination of L1+L2 proteins are currently in clinical trials.
It has been found, however, that recombinant L1 protein HPV VLPs purified from yeast are not stable during long-term storage, either in solution or when adsorbed onto aluminum adjuvant particles.
In the past, various researchers have investigated the conditions of HPV VLP assembly and disassembly. For example, McCarthy et al, 1998 "Quantitative Disassembly and Reassembly of Human Papillomavirus Type 11 Viruslike Particles in Vitro" J. Virology 72(1):32-41, describes the disassembly and reassembly of recombinant L1 HPV 11 VLPs purified from insect cells in order to obtain a homogeneous preparation of VLPs. A prolonged incubation (about 16 hours at 4.degree. C.) with a relatively high concentration of reducing agent at physiological ionic strength was used to disassemble the VLPs, and removal of the reducing agent at a higher ionic strength was used to reassemble the VLPs. This method is quite time-consuming, however.
In order to develop a commercially useful vaccine, a storage stable formulation is needed. It would be desirable to have a relatively simple, quick and quantitative treatment procedure for making a storage stable HPV VLP formulation.